The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores
The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores
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DOI：
10.1088/1478-3967/1/1/005
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发表时间：
2004-06-01
期刊：
影响因子：
2
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Beckstein, O;Sansom, MSP
如果疏水收缩位点的直径小于离子的第一水合壳的直径，则疏水收缩位点可以充当离子和水渗透的有效屏障。这种疏水性门控机制被认为在许多离子通道中起作用，例如烟碱受体、细菌机械敏感性通道（MscL和MscS）以及可能在一些钾通道（例如KcsA、MthK和KvAP）中起作用。简化的孔模型允许人们研究传导通路的主要特征，即其几何形状（形状、孔长度和半径）、孔壁表面的化学特征以及其局部柔性和表面粗糙度。我们的扩展（约0.1 μ s）的分子动力学模拟表明，一个短的疏水孔是接近水的半径小于0.45运行。通过增加孔壁的极性（并因此降低其疏水性），过渡半径可以减小，直到对于亲水性孔，液态水稳定到与水分子的半径相当的半径。离子的行为相似，但从导电孔到非导电孔的过渡甚至更陡，并且对于疏水孔发生在0.65 nm的半径处。收缩区中水蒸气的存在表明离子渗透的障碍。热力学模型可以解释水在纳米孔中的表面张力方面的行为，这导致了在这种情况下“疏水性”的简单测量。此外，增加的局部柔性降低了极性物质的渗透性。温度的升高具有相同的效果，我们假设这两种效果可以解释为有效的溶剂表面吸引力的减少，这反过来又导致溶剂壁表面自由能的增加。
A hydrophobic constriction site can act as an efficient barrier to ion and water permeation if its diameter is less than the diameter of an ion's first hydration shell. This hydrophobic gating mechanism is thought to operate in a number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA, MthK and KvAP). Simplified pore models allow one to investigate the primary characteristics of a conduction pathway, namely its geometry (shape, pore length, and radius), the chemical character of the pore wall surface, and its local flexibility and surface roughness. Our extended (about 0.1 mu s) molecular dynamic simulations show that a short hydrophobic pore is closed to water for radii smaller than 0.45 run. By increasing the polarity of the pore wall (and thus reducing its hydrophobicity) the transition radius can be decreased until for hydrophilic pores liquid water is stable down to a radius comparable to a water molecule's radius. Ions behave similarly but the transition from conducting to non-conducting pores is even steeper and occurs at a radius of 0.65 nm for hydrophobic pores. The presence of water vapour in a constriction zone indicates a barrier for ion permeation. A thermodynamic model can explain the behaviour of water in nanopores in terms of the surface tensions, which leads to a simple measure of 'hydrophobicity' in this context. Furthermore, increased local flexibility decreases the permeability of polar species. An increase in temperature has the same effect, and we hypothesize that both effects can be explained by a decrease in the effective solvent-surface attraction which in turn leads to an increase in the solvent-wall surface free energy.